Kai Zhang1-4, Xi Wu1, Zhihui Zhang1-3, Shuyu Fu1, Yurong Da1, Mei Mei1, Qi Zhang1, Yan Li1-3, Zhenyi Xue1, Lijuan Zhang1-3, Peng Zhao5* and Rongxin Zhang1-4*
1Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Basic Medical College,
2Tianjin Key Laboratory of Cellular and Molecular Immunology
3Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China
4Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China
5Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
Received: 14 July, 2015; Accepted: 01 August, 2015; Published: 05 August, 2015
Rongxin Zhang, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China, Tel: 86-22-83336563; Fax: 86-22-83336563 E-mail:
Zhang K, Wu X, Zhang Z, Fu S, Da Y, et al. (2015) Adiponectin Regulates the Development and Progression of MCA-Induced Sarcoma in Mice. Int J Immunother Cancer Res 1(1): 001-003 DOI: 10.17352/2455-8591.000001
© 2015 Bhansali Zhang K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Adiponectin; mouse sarcoma; tumor incidence
ADN: Adiponectin; MCA: Methylcholanthrene; WT: Wild Type; KO: Adiponectin Knockout Mice
Background: Sarcomas are malignant tumors with low survival rates and remain refractory to the current therapeutic methods. Adiponectin plays crucial roles in many physiological responses. Studies have shown that adiponectin could regulate various tumors. However, the roles of adiponectin in sarcomas remain unknown.
Results: In this study, we found that the adiponectin-deficient mice induced by MCA develop sarcomas more rapidly and frequently than the WT mice do. With the sarcomas formation, adiponectin deficiency showed inhibiting effect on tumor growth and reduced the mortality rates of the mice with sarcomas.
Conclusions: Adiponectin inhibits the sarcomas formation, but may promote the growth of tumor after sarcomas occur.
Adiponectin (ADN) is a type of adipocytokine and it is primarily produced by adipose tissues . Studies have shown that adiponectin plays crucial roles in many physiological responses, such as inflammation and cancer [2,3]. Many reports demonstrated that adiponectin has regulatory effects on the development and progression of various tumors via different signaling pathways [4-6]. Our previous studies also explore the potential mechanism of adiponectin on pancreatic cancer . However, the roles of adiponectin in sarcomas remain largely unknown. Sarcomas could occur in different tissues and can be divided into two major groups, namely, bone and soft-tissue sarcomas [8,9]. Sarcomas are malignant tumors with low survival rates and remain refractory to the current therapeutic methods . Therefore, it is significant to study the development, treatment and prognosis of sarcomas. Methylcholanthrene (MCA)-induced sarcoma model is a classical animal model of sarcoma and can be used to investigate the tumor immunology .
In our study, we used a low-dose MCA-induced mouse sarcoma model to explore whether adiponectin can affect the development and progression of mouse sarcoma. The results indicated that adiponectin deficiency increased the tumor incidence; in addition, the occurrence of sarcoma was earlier in contrast with the wild type (WT) mice. It is worth mentioning, after the sarcomas formation, adiponectin deficiency had been shown to have the effect of suppressing tumor growth. Mortality rates of the adiponectin-deficient mice with sarcoma were lower than the rates of the WT control group. Our data suggested that adiponectin may have inhibiting effects on the sarcomas formation, whereas, promote the tumor growth during the sarcomas progression.
Materials and methods
Female wild-type C57BL/6 mice (n=10) (Academy of Military Medical Science, Beijing, China) and female C57BL/6 background adiponectin knockout mice  (n=7) at 6 to 8 weeks old were maintained and fed in a specific pathogen-free facility at the Experimental Animal Center of Tianjin Medical University. The care for mice and the experiments were approved by Animal Ethics Committee of Tianjin Medical University and were in accordance with the guidelines for animal care.
MCA induced tumor model
Wild-type and adiponectin knockout mice were subcutaneously injected with 25 μg of MCA emulsified in corn oil  in the hind flank. For tumor development, the mice were monitored every 6 days for 156 days after the MCA induction. Tumors≥0.3cm in diameter were recorded as sarcoma positive. The tumor area was determined using the following formula: r2×3.14, where r was radius (cm) of the tumor.
The data are presented as the mean ± SD. Statistical significance was determined by a Student's t test. In the statistical comparisons, p-value < 0.05 was considered as a significant difference.
The adiponectin-deficient mice induced by MCA develop sarcomas more rapidly and more frequently than the WT mice
In this study, the adiponectin-deficient mice and the WT mice were used to induce mouse sarcoma by low-dose MCA. The mice were monitored every 6 days after the MCA induction for 156 days to observe the tumor formation and incidence. As shown in Figure 1, tumor formation of the adiponectin-deficient mice was at day 36 after the MCA induction, however, sarcomas occurred in the WT mice was later (day 60). In addition, the tumor incidence rate of the adiponection deficiency group was 71.43%, remarkably higher than the rate of the WT group (40%). These data indicated that adiponectin may have inhibiting effects on the sarcomas formation. With the deficiency of adiponectin, the mice induced by MCA developed sarcomas more rapidly and frequently in contrast with the WT mice. This suggested that adiponectin could suppress the tumor formation of sarcomas.
- Wolf AM, Wolf D, Avila MA, Moschen AR, Berasain C, et al. (2006) Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice. J Hepatol 44: 537-543.
- Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, et al. (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257: 79-83 .
- Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H (2004) Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun 323: 630-635.
- Obeid S, Hebbard L (2012) Role of adiponectin and its receptors in cancer. Cancer Biol Med 9: 213-220.
- Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, et al. (2004) Adiponectin and breast cancer risk. J Clin Endocrinol Metab 89: 1102-1107.
- Arano T, Nakagawa H, Tateishi R, Ikeda H, Uchino K, et al. (2011) Serum level of adiponectin and the risk of liver cancer development in chronic hepatitis C patients. Int J Cancer 129: 2226-2235.
- Huang B, Cheng X, Wang D, Peng M, Xue Z, et al. (2014) Adiponectin promotes pancreatic cancer progression by inhibiting apoptosis via the activation of AMPK/Sirt1/PGC-1alpha signaling. Oncotarget 5: 4732-4745.
- Sampson VB, Kamara DF, Kolb EA (2013) Xenograft and genetically engineered mouse model systems of osteosarcoma and Ewing's sarcoma: tumor models for cancer drug discovery. Expert Opin Drug Discov 8: 1181-1189.
- Helman LJ, Meltzer P (2003) Mechanisms of sarcoma development. Nat Rev Cancer 3: 685-694 .
- Foley EJ (1953) Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res 13: 835-837 .
- Ma K, Cabrero A, Saha PK, Kojima H, Li L, et al. (2002) Increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J Biol Chem 277: 34658-34661 .
- Wu X, Peng M, Huang B, Zhang H, Wang H, et al. (2013) Immune microenvironment profiles of tumor immune equilibrium and immune escape states of mouse sarcoma. Cancer Lett 340: 124-133 .
- Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, et al. (2005) Prostate cancer and adiponectin. Urology 65: 1168-1172 .
- Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, et al. (2005) Plasma adiponectin and gastric cancer. Clin Cancer Res 11: 466-472 .
- Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS (2005) Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst 97: 1688-1694 .
- Vielma SA, Klein RL, Levingston CA,Young MR (2013) Adipocytes as immune regulatory cells. Int Immunopharmacol 16: 224-231 .
- Piccio L, Cantoni C, Henderson JG, Hawiger D, Ramsbottom M, et al. (2013) Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis. Eur J Immunol 43: 2089-2100 .
- Tsang JY, Li D, Ho D, Peng J, Xu A, et al. (2011) Novel immunomodulatory effects of adiponectin on dendritic cell functions. Int Immunopharmacol 11: 604-609 .
- Vakkila J, Lotze MT (2004) Inflammation and necrosis promote tumour growth. Nat Rev Immunol 4: 641-648 .
- Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454: 436-444 .
- Prehn RT, Main JM (1957) Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst 18: 769-778 .
- Kono K, Petersson M, Ciupitu AM, Wen T, Klein G, et al. (1995) Methylcholanthrene-induced mouse sarcomas express individually distinct major histocompatibility complex class I-associated peptides recognized by specific CD8+ T-cell lines. Cancer Res 55: 5648-5655 .
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